The three projects of this Program Project deal with several areas that affect blood service care. Immunity to hepatitis B virus surface antigen (HbsAg), natural killer, T and dendritic cell function, and the genetic basis of selective deficiency of IgA. Its component projects use conserved extended major histocompatibility complex (MHC) haplotypes to explore control by these genes in each area of study. The projects are supported by an Administrative Core and a Blood Cell Separation and MHC Typing Core. Project 7 studies the genetic and cellular bases for response or nonresponse to HbsAg and seeks to understand the early events in response and nonresponse. Therefore, this project will explore T helper and T cell cytotoxic responses in naive subjects, nonresponders and responders with varying degrees of response. The ability of dendritic cells to induce a primary immune response to HbsAg in naive T cells in vitro and to predict ultimate response by naive individuals in vivo will be tested. Project 8 will study the role of HLA-B/C and MICA alleles in determining NK subsets and the expression of inhibitory and activating NK receptors by individual uncloned NK cells. Project 9 will localize the chromosomal regions of the MHC for susceptibility genes for IgA deficiency and related immunoglobulin deficiency states. A general genetic model, including the participation of non-MHC genes, will be developed. The hypothesis that incomplete penetrance in these disorders is related to variation in susceptibility gene expression will be tested.